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Relationship between adrenal fatigue and glutamate release / NMDA hyperactivation

Discussion in 'Adrenal Dysfunction' started by hixxy, Feb 7, 2012.

  1. PokerPlayer

    PokerPlayer Guest

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    I've tried everything on that list but Memantine. I think you should put klonopin on that list right!?

    Also, curcumin seemed to help depression and mental anxiety but it felt really stimulating to the body, it felt like maybe it was hard on my body.... I would like to try it out for a while but am not sure.
  2. adreno

    adreno 3% neanderthal

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    I don't know. It has anticonvulsant properties, and increases gaba levels, but long term use of benzodiazepines are known to lead to cognitive impairment. I wouldn't take it long term, except as a last resort.

    http://www.ncbi.nlm.nih.gov/m/pubmed/14731058/
  3. adreno

    adreno 3% neanderthal

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  4. PokerPlayer

    PokerPlayer Guest

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  5. Lotus97

    Lotus97 Senior Member

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    I am relatively certain that my hypoglycemic symptoms are from malfunctioning adrenals. I haven't had my adrenals fully tested, but my cortisol tested to be both too high and too low. Adrenal fatigue is a bit of a misnomer since some times it can be overstimulation caused by high cortisol or low cortisol and high norepinephrine.
  6. jeffrez

    jeffrez Senior Member

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    The reason for the paradoxical meditation results could be related to the overall adrenal (hpaa) problem. I get the same thing, but with panic attacks 8 hours later - like you say, almost like clockwork. What I've found out about this that helps explain it is related to the entire subject of HPAA/stress, etc.

    The body strives to maintain a homeostatic balance between sympathetic and parasympathetic systems. Normally, this balance has a certain set point, let's just call it ground zero. During a stressful event, the sympathetic system gets cranked up in the "fight or flight" (FOF) response in characteristic ways - increased heart rate and blood pressure, blood diverted away from digestion and to the muscles, etc. After the stress, the body then resets the sympathetic response back down to the baseline level to return to homeostasis.

    With chronic stress, however, the basic set point of both systems gets raised. The system has been stressed so continuously that the parasympathetic starts rising to meet the sympathetic, and gradually creates a new, higher baseline. So for a moderately long-term stressor, the set point goes from "ground zero" to let's say arbitrarily 20. Now not only is the threshold for triggering FOF much lower, meaning it will take relatively less stimulus to crank you up into FOF, but you won't return all the way down to ground zero anymore after the stress, but will just go back to that new set point of 20, where your body now "lives."

    What's happening with meditation is actually the reverse of that process. When triggering the relaxation response, it's now the *parasympathetic* system that's getting cranked up, which as the name Benson gave it indicates, has the effect of relaxing the body. During meditation, therefore, and for a while afterward, you feel great. But then what happens is that the brain/body perceives this condition as also being homeostatically imbalanced, and it will strive to regain balance, in this case by cranking up the *sympathetic* system in a kind of boomerang or rebound effect to match or balance out the elevated parasympathetic response. The brain doesn't really know (or care) about which way the imbalance is, all it knows is that it's out of balance and that it needs to be restored by any means necessary.

    Apparently with these chronic stress/fatigue conditions, the HPAA is so much more delicate that it's easier to miss the mark and overshoot the response, so the sympathetic overdoes it and gets too elevated. The result is heightened anxiety or panic, elevated cortisol leading to depression, etc. Then eventually that calms down, and then you're back at square one, or in the earlier model, square 20. Except now you're probably cranked up to 25, lol.

    The answer might just be to meditate for shorter sessions, so that you're getting only a milder increase in the parasympathetic that won't be enough to rebound the sympathetic past the mark and cause the excess symptoms. Then gradually as the set point of both gets lower, the sessions could probably be increased without provoking the negative effects of rebounding sympathetic response.

    Regarding the klonopin, etc., the benzos are GABAergic, and there are a lot of anxiolytic herbs that have similar actions: passiflora, melissa, valerian, etc. One or more of those combined might possibly at least help extend the time between having to take the klonopin. It seems that your system is very sensitive to sympathetic arousal, and as that slowly rises over a few days back to the set point after taking the klonopin you're getting symptoms. Combining a "titrated" meditation approach with some of the GABA herbs might help you reset the system lower again and stay off the benzos for good.
  7. Lotus97

    Lotus97 Senior Member

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    Overmethylation can also cause excitoxicity so supplements such as methylcobalamin and P5P should be used cautiously.
  8. Lotus97

    Lotus97 Senior Member

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    There's a thread about NMDA, ammonia, and anxiety. It has a lot of useful tips about how to deal with NMDA and anxiety. It also talks about how ammonia can activate NMDA receptors.
    http://forums.phoenixrising.me/index.php?threads/anxiety-ammonia-and-the-nmda-receptor.1460/
    This from Hip:
    The question is: What is the anxiety axis, and what biochemical pathway(s) are over-revving it?

    I think the answer may lie, at least in part, in the NMDA receptors in the brain. It is well-known that the NMDA receptors found on neurons mediate anxiety behavior. Normally, the NMDA receptor is stimulated (switched on) by the brain's neurotransmitter glutamate. However, a number of other substances can also switch on the NMDA receptor.

    Presumably, any foreign chemical substance in the body that can stimulate the NMDA receptors, and that can cross the blood-brain barrier, will potentially generate a constant "wired" or high anxiety state. Such anxiety states will be generated irrespective of life circumstances: it is not a normal psychologically-produced anxiety, but biochemically-generated anxiety - and thus one you cannot directly control.

    Now, one chemical substance that is a HIGHLY POTENT activator of the NMDA receptors is ammonia. Ammonia can be produced in the body by various pathological processes, and it can cross the blood-brain barrier very easily.

    Many bacteria can produce ammonia. One example is proteus mirabilis, commonly found in in the gut/kidneys of people with urinary tract infections. Proteus mirabilis produces an enzyme called urease, which converts urea into ammonia. (Incidentally, Proteus mirabilis is also a sulfur-reducing bacterium that can produce H2S). There are other species of bacteria that can also produce urease, and so may potentially produce ammonia.

    So I wonder if there is another gut/kidney - brain connection in CFS, via ammonia produced in the gut or kidenys, that underpins the "wired but tired" and anxiety states of CFS.

    Interestingly, high-dose magnesium - one of the classic CFS palliatives - is a good blocker of NMDA receptor activation. I expect that is why magnesium is a calming supplement in general. Other blockers of NMDA activation (NMDA antagonists) include: zinc, taurine, progesterone, cats's claw (possibly), guaifenesin (possibly) and the drugs: memantine, ketamine, riluzole, dextromethorphan, amantadine, and also more obscure ones: nitrous oxide, xenon gas, and ibogaine.

    As many CFS patients can testify, these supplement can all help in reducing the "wired but tired"/anxiety state. The mental tiredness may arise, in part, from the NMDA overestimation itself, which exhausts the brain cells (and can cause brain cell death by excitotoxicity).

    But if ammonia is contributing to CFS symptoms (a big if), then rather than just trying to block the NMDA receptor with magnesium etc, perhaps there might be ways of stopping ammonia being produced at source (that is, tackling any ammonia-producing bacteria in the gut, kidneys, or perhaps even sinuses).
  9. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Adrenal fatigue or probably more appropriately called adrenal dysfunction i think is real but the explanation behind it isnt quite right. Its not the adrenals fatigue but the signalling from the hypothalamus has gone wrong??

    Cortisol has a stabilizing affect of blood sugar levels, so it can cause issues with hypoglycaemia etc. Sometimes i dont think its a matter of low or high cortisol but inappropriate cortisol response or rhthym. This also can mess sleep cycle up alot i think think more important in controlling sleep then circadian rhthym, which i think is why many dont fully respond to melatonin.

    I think its worth persuing but not always straight forward, so takes some tinkering with it to get it sorted??

    cheers!!
  10. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    dextromethorphan a common ingredient in cough medicine and is an nmda antagonist. There has been a study on it with fibromyalgia that looked promising. It is also mentioned on some sites for helping reverse benzo tolerance, i have used this in 30mg dose which is the recommended dose on the bottle and it seems to help benzo's to work better. I use it for say a month every night when i feel sleep meds arent working as well. It has also helped me sometimes for nerve/skin type pain and times when i have had headaches when nothing seems to shift it, but i find it can be hit and miss for these things?? Good thing about it is its cheap and easily available etc.

    cheers!!!
  11. Lotus97

    Lotus97 Senior Member

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    Although dextromethorphan (aka DXM) is probably safe at therapeutic dosages, it's worth mentioning that an overdose is fatal. Something about the body overheating.
  12. Lotus97

    Lotus97 Senior Member

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    My wired periods seemed to come after periods of fatigue and/or PEM. Getting a lot of sleep and limiting activities seem to help a lot, but it's easier said than done. The medication I was on during my last recovery caused me to gain 30 lbs and raised my cholesterol. And when I'm wired I can't seem to stay in bed. So far, treatments recommended for NMDA haven't seemed to help. I'm going to start Remeron tonight for sleep. Hopefully that will help. I'm actually more relaxed when I get a lot of sleep and when I don't sleep well I'm more amped up. And during the day when I'm at the computer I'm more wired afterwards, but if I'm able to stay in bed I end up relaxed. Someone suggested that could be from low cortisol and high norepinephrine. The last time my cortisol was tested was 4 years ago so I have no clue what's going on. Last year during my recovery when I was in bed much of the day my doctor wanted to give me stimulants, but now she doesn't seem to want to do much. Hopefully the Remeron will help.
  13. Lotus97

    Lotus97 Senior Member

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    I was reading that norepinephrine can lower GABA. If a person with adrenal dysfunction has low cortisol then low cortisol can cause high NE. If the high NE lowers GABA then that would increase the effects NMDA stimulation.
    heapsreal likes this.

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